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- Member of: Theses and Dissertations
Environmental and genetic factors influence schizophrenia risk. Individuals who have direct family members with schizophrenia have a much higher incidence. Also, acute stress or life crisis may precede the onset of the disease. This study aims to understand the effects of environment on genes related to schizophrenia risk. It investigates the impact of sleep deprivation as an acute environmental stressor on the expression of Htr2a in mice, a gene that codes for the serotonin 2A receptor (5-HT2AR). HTR2A is associated with schizophrenia risk through genetic association studies and expression is decreased in post-mortem studies of patients with the disease. Furthermore, sleep deprivation as a stressor in human trials has been shown to increase the binding capacity of 5-HT2AR. We hypothesize that sleep deprivation will increase the number of cells expressing Htr2a in the mouse anterior prefrontal cortex when compared to controls. Sleep deprived that mice express EGFP under control of the Htr2a promoter displayed anteroposterior gradients of expression across sagittal sections, with concentrations seen most densely within the prefrontal cortex as well as the anterior pretectal nucleus, thalamic nucleus, as well as the cingulate gyrus. Htr2a-EGFP expression was most densely visualized in cortical layer V and VI pyramidal neurons within the lateral prefrontal cortex of coronal sections. Furthermore, the medial prefrontal cortex contained significantly cells expressing Htr2a¬-EGFP than the lateral prefrontal cortex. Ultimately, the hypothesis was not supported and sleep deprivation did not result in more ¬Htr2a-EGFP expressing cells compared to basal levels. However, expressing cells appeared visibly brighter in sleep-deprived animals when compared to controls, indicating that the amount of intracellular Htr2a-GFP expression may be higher. This study provides strong visual representations of expression gradients following sleep deprivation as an acute stressor and paves the way for future studies regarding 5H-T2AR’s role in schizophrenia.
To determine if Egr3 alters Htr2a transcription under stress, I examined messenger ribonucleic acid (mRNA) levels of these two genes in wildtype (WT) and Egr3 -/- mice after 6hrs of sleep deprivation (SD). I found both genes are increased in WT mice after SD compared with controls. In addition, Egr3 is required for Htr2a induction because SD fails to induce Htr2a expression in Egr3 -/- mice. Next, I performed chromatin immunoprecipitation (ChIP) to determine if EGR3 binds to Htr2a promoter in vivo. I found a significant increase of EGR3 binding to Htr2a distal promoter 2hrs after seizure. To determine the functionality of this binding, I co-transfected the CMV- EGR3 vector or CMV- vector alone with the Htr2a distal promoter reporter clone. I found overexpression of EGR3 activates the Htr2a distal promoter-driven luciferase gene. Although the ChIP assay shows no direct binding of EGR3 to Htr2a proximal promoter, I found EGR3 overexpression activates Htr2a proximal promoter-driven luciferase gene. These findings suggest that EGR3 regulates Htr2a probably through both direct and indirect ways.
Pediatric anxiety disorders are highly prevalent and while pharmacological intervention seems to be an effective treatment, the validity of reported adverse side effects remains unclear. <br/><br/>Objective: To analyze the nature of evidence regarding adverse side effects in the pharmacological treatment of pediatric anxiety disorders. <br/><br/>Approach: A search using Google Scholar, PubMed, and PsychInfo was conducted for meta-analyses of pharmacological treatment of pediatric anxiety disorders as well as randomized controlled trials. The focus was on adverse events.<br/><br/>Results and Conclusion: Reportings of a limited number of adverse events were found among resources available to clinician and patient informed sources to inform pharmacological treatment of pediatric anxiety disorders. Only a small fraction of adverse side effects were found in the research literature. This finding raises concerns about making informed decisions to treat pediatric anxiety disorders with pharmacotherapy.
The thesis project merges interdisciplinary research to develop a self-directed creative intervention for immigrant youth, allowing them to make sense of their social and cultural identities. It takes research on self-awareness, multicultural identification, perceived belonging, and bibliotherapy to create a guided journal titled "Unearth," filled with art and writing prompts that are age-appropriate for adolescents and that serve as avenues for self-exploration. The project ultimately engages a focus group discussion to understand the usability and accessibility of the intervention.
The thesis project merges interdisciplinary research to develop a self-directed creative intervention for immigrant youth, allowing them to make sense of their social and cultural identities. It takes research on self-awareness, multicultural identification, perceived belonging, and bibliotherapy to create a guided journal titled "Unearth," filled with art and writing prompts that are age-appropriate for adolescents and that serve as avenues for self-exploration. The project ultimately engages a focus group discussion to understand the usability and accessibility of the intervention.